A substantial body of evidence supports the relationship between 5-HT.sub.2 receptor modulation and a variety of diseases and conditions. The 5HT.sub.2 receptor class, as used herein, generically includes 5-HT.sub.2A, 5-HT.sub.2B, and/or 5-HT.sub.2C receptors. The specific 5-HT.sub.2 receptor subtypes are named when a specific subtype is intended.
The activation of the 5-HT.sub.2 receptor has been associated with numerous behavioral and physiological effects. TiPS, 11, 181 (May 1990). The 5HT.sub.2 receptors in the limbic system can affect mood, behavior, and hallucinogenesis. Hartig et al., The 5-HT.sub.1C Receptor Annals New York Academy of Science, 149, 159. Modulation of the 5HT.sub.2 receptors has been associated with schizophrenia and schizophreniform disorders. Ugedo, L. et al. Psychopharmacology, 98, 45 (1989); Canton H. et al. Eur, J, Pharmacol., 191, 93 (1990). Hypothalamic 5-HT.sub.2 receptors can influence sleep, appetite, thermoregulation, sexual behavior, motor activity, and neuroendocrine function. Hartig et al., The 5-HT.sub.1C Receptor Annals New York Academy of Science, 149, 159. Additionally, studies indicate that 5-HT.sub.2 receptors mediate hypoactivity, caused decreased feeding in rats, and have anxiogenic effects. Id. Studies have shown that drug-induced penile erections are 5-HT.sub.2 mediated. Psychopharmacology, 101, 57 (1990). Likewise, 5-HT.sub.2 modulation can treat or prevent priapism.
Studies evince that 5-HT.sub.2 receptors influence the onset of anxiety, obsessive-compulsive disorders, panic disorders, Gilles de la Tourette syndrome and migraine headaches. TiPS, 11, 181 (May 1990). The studies indicate that the 5-HT.sub.2 receptor can be involved in Alzheimer's disease as well. Id. The 5-HT.sub.2 receptor is involved in the modulation of the balance of cerebrospinal fluid. Further, the 5-HT.sub.2 receptor is associated with the sensation of pain. Zemlan, F. P. et al. Neurochem, Int., 16, 507 (1990).
Further, compounds having affinity and selectivity for the 5HT.sub.2 receptor can be useful for treating a variety of conditions related to 5HT.sub.2A, 5HT.sub.2B, and/or 5HT.sub.2C modulation. For example, compounds useful for the modulation of the 5HT.sub.2B receptor are useful for treating patients suffering from or susceptible to ichlasia, hypertonic lower esophogeal sphincter, tachygastria, hypermotility associated with irritable bowel syndrome, constipation, dyspepsia, and other 5-HT.sub.2B related conditions. Additionally, modulation of the 5HT.sub.2 A receptor has been associated with schizophrenia, anxiety, depression, and migraines. Koek, W. Neuroscience and Biobehavioral Reviews, 16, 95-105 (1992).
It would be advantageous to have compounds which would permit modulation of the 5-HT.sub.2A, 5HT.sub.2B, and/or 5HT.sub.2C receptors. It would be particularly desirable to have compounds with high 5-HT.sub.2 receptor subtype affinity and selectivity. It would be further advantageous to have compounds that minimize the effects of eating disorders, sexual disorders, and other disorders or conditions associated with 5-HT.sub.2 receptor subtype modulation.